Metabolism
A Little Biology
Animals rely on energy from the sun to do work.
Light energy to
chemical bond
energy.
reduce CO2  glucose
Plants
Heterotrophs or
chemotrophs (that’s
us) extract energy in
the form of chemical
bond energy to do
work.
oxidize glucose  CO2
Animals
The Big Picture
Ultimately the carbon
atoms from glucose
 CO2
Biochemists like to
use the word “fate”
for “what happens
to”.
In the conversion of
glucose to CO2 energy
is extracted in the form
of chemical bond
energy in discrete
steps.
What is the fate of
glucose under
aerobic conditions?
What is the fate of
pyruvate during
strenuous exercise?
What is the fate of
medical students after
their biochemistry final
exam?
Metabolism
• The sum total of all the chemical and physical
changes that occur in a living system , which
may be a cell, a tissue, an organ, or an
organism.
– The reactions of metabolism are almost all enzymecatalyzed.
• transformation of nutrients
• excretion of waste products
• energy transformations
• synthetic and degradative processes
Catabolism vs. Anabolism
• Catabolism is the phase of metabolism
that encompasses the breaking down and
energy yielding reactions.
• The cellular breakdown of complex
substances and macromolecules
Catabolism vs. Anabolism
• Anabolism is the phase of metabolism that
encompasses the making of biological
molecules and require energy.
• The cellular synthesis of complex
substances and macromolecules smaller
molecules.
The Really Big Picture
The Stages of Cellular
Metabolism: A Preview
• Metabolic Respiration is a cumulative
function of three metabolic stages
– Glycolysis
– The citric acid cycle
– Oxidative phosphorylation
• Glycolysis (glyco= glucose and lysis= split)
– Breaks down glucose into two molecules of
pyruvate
• The citric acid cycle
– Completes the breakdown of glucose
• Oxidative phosphorylation
– Is driven by the electron transport chain
– Generates ATP (Cell energy)
2H
1/
+
2
O2
(from food via NADH)
2 H+ + 2 e–
Controlled release
of energy for
synthesis of
ATP
Free energy, G
ATP
ATP
ATP
2 e–
1/
2
H+
H2O
Figure 9.5 B
(b) Cellular respiration
2
O2
• A animal cell
ENDOPLASMIC RETICULUM (ER)
Nuclear envelope
Nucleolus
Rough ER
NUCLEUS
Smooth ER
Chromatin
Flagelium
Plasma membrane
Centrosome
CYTOSKELETON
Microfilaments
Intermediate filaments
Ribosomes
Microtubules
Microvilli
Golgi apparatus
Peroxisome
Figure 6.9
Lysosome
Mitochondrion
In animal cells but not plant cells:
Lysosomes
Centrioles
Flagella (in some plant sperm)
• Mitochondria are enclosed by two
membranes
– A smooth outer membrane
– An inner membrane folded into cristae
Mitochondrion
Intermembrane space
Outer
membrane
Free
ribosomes
in the
mitochondrial
matrix
Inner
membrane
Cristae
Matrix
Figure 6.17
Mitochondrial
DNA
100 µm
• An overview
of cellular respiration
Electrons carried
Electrons
via NADH and
FADH2
carried
via NADH
Glycolsis
Pyruvate
Glucose
Cytosol
ATP
Figure 9.6
Substrate-level
phosphorylation
Citric
acid
cycle
Oxidative
phosphorylation:
electron
transport and
chemiosmosis
Mitochondrion
ATP
Substrate-level
phosphorylation
ATP
Oxidative
phosphorylation
• Both glycolysis and the citric acid cycle
– Can generate ATP by substrate-level
phosphorylation
Enzyme
Enzyme
ADP
P
Substrate
+
Figure 9.7
Product
ATP
• Glycolysis harvests energy by oxidizing
glucose to pyruvate
• Glycolysis
– Means “splitting of sugar”
– Breaks down glucose into pyruvate
– Occurs in the cytoplasm of the cell
• Glycolysis consists of two major phases
– Energy investment phase
– Energy payoff phase
Glycolysis
ATP
Citric
acid
cycle
Oxidative
phosphorylation
ATP
ATP
Energy investment phase
Glucose
2 ATP + 2
P
used
2 ATP
Energy payoff phase
4 ADP + 4
P
2 NAD+ + 4 e- + 4 H +
4 ATP
formed
2 NADH
+ 2 H+
2 Pyruvate + 2 H2O
Glucose
4 ATP formed – 2 ATP used
Figure 9.8
2 NAD+ + 4 e– + 4 H +
2 Pyruvate + 2 H2O
2 ATP
+ 2 H+
2 NADH
• Before the citric acid cycle can begin
– Pyruvate must first be converted to acetyl
CoA, which links the cycle to glycolysis
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
O–
S
CoA
C
O
2
C
C
O
O
1
3
CH3
Pyruvate
Transport protein
Figure 9.10
CH3
Acetyle CoA
CO2
Coenzyme A
• An overview of the citric acid cycle
Pyruvate
(from glycolysis,
2 molecules per glucose)
Glycolysis
Citric
acid
cycle
ATP
ATP
Oxidative
phosphorylatio
n
ATP
CO2
CoA
NADH
+ 3 H+ Acetyle CoA
CoA
CoA
Citric
acid
cycle
2 CO2
3 NAD+
FADH2
FAD
3 NADH
+ 3 H+
ADP + P i
ATP
Figure 9.11
• There are three main processes in this
metabolic enterprise
Electron shuttles
span membrane
CYTOSOL
MITOCHONDRION
2 NADH
or
2 FADH2
2 NADH
2 NADH
Glycolysis
Glucose
2
Pyruvate
2
Acetyl
CoA
+ 2 ATP
by substrate-level
phosphorylation
Maximum per glucose:
Figure 9.16
6 NADH
Citric
acid
cycle
+ 2 ATP
2 FADH2
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
+ about 32 or 34 ATP
by substrate-level by oxidative phosphorylation, depending
on which shuttle transports electrons
phosphorylation
from NADH in cytosol
About
36 or 38 ATP
• The catabolism of various molecules from
food
Proteins
Amino
acids
Carbohydrates
Sugars
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Citric
acid
cycle
Figure 9.19
Oxidative
phosphorylation
Fats
Glycerol
Fatty
acids
• The control of cellular respiration
Glucose
AMP
Glycolysis
Fructose-6-phosphate
–
Inhibits
Phosphofructokinase
Fructose-1,6-bisphosphate
+
Stimulates
–
Inhibits
Pyruvate
Citrate
ATP
Acetyl CoA
Citric
acid
cycle
Figure 9.20
Oxidative
phosphorylation
ATP
• Chemical energy of the cell
• The cell takes up glucose and converts it
to cell energy (ATP)
• Various forms of cell energy
– ATP, ADP, AMP, Creatine phosphate
The structure of ATP, ADP, and
AMP
adenine
ribose
ATP is most commonly
hydrolyzed to ADP or
AMP
The structural Basis of High
Phosphoryl Transfer Potential of
ATP
Creatine phosphate is a reservoir of high potential
phosphoryl groups. Creatine kinase transfers
phosphate to ADP to form ATP. This reaction is
important in heart muscle after an Myocardial
Infarction.
Other Activated Carriers
• Just as ATP carries and transfers
phosphate other molecules carry electrons
and participate in oxidation reduction
reactions (i.e. NADH, NADH2, FADH2).
The electrons
are not directly
transferred to
O2.
Electron carriers (i.e.
NADH)
Deliver Energy
To ETS
Electron Transfer System
Nicotine Adenine Dinucleotide
NADPH
Generally, NAD+ participates in
reactions where alcohols are
converted to ketones/aldehydes and
organic acids.
Synthetic and degradative pathways are distinct.
If [ATP] is low, degradative pathways are stimulated.
If [ATP] is high, degradative pathways are inhibited.
Degradation
Synthesis
Regulation of the degradation and synthesis of glucose and
glycogen depends on the energy state of the cell
•High [NADH] is indirectly equivalent to
high[ATP]. This means that the cell is high
in “energy”.
•High [NAD+] or [ADP or AMP] means that
the cell is low in “energy”.
•These molecules (and others) can act as
allosteric effectors stimulating or inhibiting
allosteric enzymes which are usually at the
beginning or branch-points of a specific
pathway.
Synthetic and Degradative
Pathways Don’t Happen at the
Same Time
• They can share some common steps but
they are never simply the reverse of one
another.
• Synthetic pathways always use more ATP
than a degradative pathway will produce.
• If both synthetic and degradative pathways
occurred at the same time, “wasteful”
hydrolysis of ATP would result.
• This is termed a “futile cycle.”
Regulation of synthetic and
degradative pathways.
• For example, phosphorylation activates
glycogenolysis (breakdown of glucose)
whereas phosphorylation inactivates
glycogenesis (glycogen synthesis).
• Put differently: Phosphorylation activates
glycogenolysis whereas dephosphorylation
activates glycogenesis.
• On the same theme, the action of insulin is
opposite to that of glucagon.
• Insulin decreases blood glucose levels
whereas glucagon increases blood glucose
levels.
In Summary
Intrinsic Regulation
• Molecules such as NAD+, NADH, ATP, ADP,
AMP etc. are important intrinsic regulators of
cellular metabolism.
– the concentrations of these molecules mirror the
energy charge of the cell and act as regulators of
the cells’ metabolism.
This is only one level of regulation.
Extrinsic Regulation
• Hormones are a higher order of regulation
involving communication between cells,
tissues, and the environment.
• Many hormones (not all) interact with cell
surface receptors and set off a cascade of
molecular events which:
 stimulate or repress the activity of key enzymes.

AND/OR
 stimulate or repress the transcription of specific
genes.
• Two hormones that are of particular
importance and involve the regulation of
catabolic and anabolic pathways are:
INSULIN
&
GLUCAGON
Insulin vs. Glucagon
• In general:
– Insulin operates through dephosphorylation
mechanisms.
– Glucagon operates through phosphorylation
mechanisms.
A fatty acid molecule (subunit of fat) is in
a more reduced state than a molecule of
glucose.
Thus, more
energy is
extracted from
the FA than
CHO.
What’s Next?
• The endocrine lectures will deal with the
degradation and synthesis of carbohydrates.
• This will be followed by lectures dealing with
the degradation and synthesis of fatty acids.
• Some integrative of metabolism will then be
discussed within a frame work of “feeding, fasting, and exercising”